She was born Anne Ward in Holborn, London, England. She married William Radcliffe, an editor for the English Chronicle, at Bath in 1788. To amuse herself, she began to write fiction, an avocation her husband encouraged.
She published The Castles of Athlyn and Dunbane in 1789. This set the tone for the majority of her work, which tended to involve innocent, but heroic young women who find themselves in gloomy, mysterious castles ruled by even more mysterious barons with dark pasts.
Her works were extremely popular, especially with respectably sheltered young women who were starved for something a bit more exciting than needlepoint. Her works included The Sicilian Romance, The Romance of the Forest, The Mysteries of Udolpho, and The Italian.
She died on February 7, 1823, probably of an attack of asthma.